PATTERN OF HEMATOLOGICAL DISEASES IN HOSPITALIZED PAEDITRIC PATIENTS BASED ON BONE MARROW EXAMINATION

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1 ORIGINAL ARTICLE PATTERN OF HEMATOLOGICAL DISEASES IN HOSPITALIZED PAEDITRIC PATIENTS BASED ON BONE MARROW EXAMINATION Afzal Khan, Muhammad Aqeel, Taj Ali Khan, Arshia Munir Department of Pediatrics and Department of Hematology, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan ABSTRACT Objective: The objective of this study was to look into various diagnoses of hematological lesions on bone marrow examination in our paediatric age group of patients. Material and Methods: This study was conducted in the Pediatric A Unit and Department of Hematology Postgraduate Medical Institute (PGMI) Lady Reading Hospital, Peshawar from 01st Jan 2007 to 31st Dec Children admitted with pallor, bleeding, lymphadenopathy or visceromegaly having abnormal smear results were included in this study. The data was statistically analyzed by SPSS version 10. Results: One hundred and ninety-eight cases were included in the study. The age range was from 06 months to 14 years with a mean age of 5.35 years and standard deviation of ± Majority (47.5%) of these children were in the age range of 1 to 5 years with male to female ratio of The commonest disorder was aplastic anemia present in 40 (20.2%) of the cases followed by idiopathic thrombocytopenic purpura (ITP) (15.7%), megaloblastic anemia (14.6%) and iron deficiency anemia (7.6 %). Acute leukemia was the predominant malignant disorder present in 11.6% of the cases. There were also few cases of histiocytosis and bone marrow secondaries. Visceral leishmaniasis, anemia of chronic disorders, haemolytic anemia, myeloid hyperplasia, hypersplenism, congenital dyserythropoietic anemia, malaria and Gaucher disease were the other non-malignant hematological disorders found in this study. Conclusion: Aplastic anemia, idiopathic thrombocytopenic purpura, megaloblastic anemia and leukemia are the commonest hematological disorders in our set up. Key Words: Bone Marrow Examination, Aplastic Anemia, Megaloblastic Anemia, Leukemia INTRODUCTION evaluated for possibility of either a bone marrow failure syndrome or acute malignancy, particularly Hematological disorders are quite common in when associated with lymphadenopathy or children. These vary from simple conditions like visceromegaly. iron deficiency anemia to congenital hypoplastic anemia and physiological anemia of infancy to Megaloblastic anemia secondary to vitamin B12 acquired red cell aplasia. Pancytopenia is a and Folate deficiency can lead to peripheral frequently occurring condition in this age group. It cytopenia. These children present with anemia, may be a transient event secondary to viral b leeding f r o m the s k in and mucosa and infection like parvovirus B19 or something grave vulnerability to infections. Myelodysplastic like congenital bone marrow aplasia1. This can syndrome is another acquired disorder in which the also result from either a failure of production of bone marrow fails to produce and release sufficient hematopoietic progenitor cells, called aplastic blood cells.9 Leukemia is the most frequently anemia or peripheral destruction of cellular occurring malignancy in children and requires elements either due to infection, immune mediated bone marrow examination for diagnosis. damage or hypersplenism.2 Even simple drugs like Bone marrow aspiration and examination is one of the albendazole can lead to pancytopenia.3 Bone important diagnostic procedures for many hematological marrow replacement by storage cells like Gaucher disorders.10 This procedure is increasingly useful in or malignant cells can also lead to this problem.4 documenting metastatic involvement of tumors like The same is true with visceral leishmaniasis.5,6 neuroblastoma.11 There is wide variety of disorders in Bacterial infection like Brucellosis can lead to paediatric patients where bone marrow examination pancytopenia in this age group.7,8 Clinically a 12 provides diagnostically important informations. child presenting with pancytopenia should be 196

2 Statistics Mean (years) Std. Error Std Deviation Minimum Maximum Median Mode Liquid bone marrow is aspirated from the tibia or posterior iliac crest under local anesthesia with little discomfort to the patient. Trephine biopsy is usually performed when there is hypoplasia or aplasia on 13 aspiration. There is a long list of diseases which reveal bone marrow changes. A large number of these disorders present with vague clinical symptoms and create a diagnostic problem which cannot be solved without resorting to bone marrow aspiration and examination. Furthermore the spectrum of hematological disorders is relatively different in the 14 developing world than the developed countries. Therefore, this study was conducted with the view to know the etiological spectrum of disorders diagnosed on bone marrow examination MATERIAL AND METHODS This study was conducted at the Pediatric A Unit and Department of Hematology, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar over a period of one year. All the patients above one month of age and below fifteen y e a r s a d m i t t e d w i t h p a l l o r, b l e e d i n g, lymphadenopathy or hepatosplenomegaly, having abnormalities on peripheral blood smear were included the study. Detailed clinical history was recorded especially relating < >10 Total Table 1 AGE GROUP Table 2 Age of the patients in years ± Age in Years Frequency Percent to age, sex, presenting complaints (fever, pallor, bleeding from skin or mucus membrane, or jaundice etc). These patients were then examined for anemia, jaundice, purpura, lymphadenopathy and hepatosplenomegaly. Bone marrow aspiration was done under local anesthesia from the upper end of the tibia in children less than 02 years of age and from posterior iliac crest in those above the age of 02 years. Bone marrow trephine biopsy was performed in selected cases in the department of hematology, Lady Reading Hospital, Peshawar. Slides were made and then processed by hematologist. The data was analyzed using SPSS version 10, for variables. RESULTS One hundred and ninety-eight cases were included in the study. The age range was from 06 months to 14 years with a mean age of 5.35 ± 3.7 years (table 1). Majority of these children were in between the ages of 1 to 5 years (47.5%) followed by age range 5 to 10 years (35.9%) {Table 2}. Males were 120 (60.6%) while females were 78 (39.4%) with a male to female ratio of 1.53 (table 3). Aplastic anemia was the most common disorder present in 40 (20.2%) cases followed by idiopathic thrombocytopenic purpura [ITP] (15.7%), megaloblastic anemia (14.6%) and iron deficiency anemia (7.6 %). Other non malignant disorders like visceral leishmaniasis, anemia of chronic disorder, haemolytic anemia, myeloid hyperplasia, hypersplenism, congenital dyserythropoietic anemia, malaria and Gaucher disease were also diagnosed in this study. Acute leukemia was the predominant malignant disorder present in 11.6% of the cases. There were also few cases of histiocytosis and bone marrow secondaries (table 4). Majority of theses patients presented with anemia, bleeding from mucus membrane or into the skin. Patients with malignancy had various degrees of splenomegaly (79.2%), hepatomegaly (60.9%) and lymphadenopathy (39.1%) as well. DISCUSSION Hematological diseases are frequently encountered in paediatric practice. Bone marrow examination is one of the important investigations to clinch the final diagnosis. In our study three non malignant disorders i.e. hypoplastic or aplastic anemia, ITP, megaloblastic anemia; and leukemia (one of the malignant condition) emerged the most common entities, present in 62.1% of the total cases. Similar results have been reported in a recent study from Peshawar.13 Aplastic anemia was the most common disorder present in 20.2 % of these patients. It is more common in developing countries as compared to the industrialized world.14, 15 Its exact incidence is unknown in our country due to lack of realistic community based studies, however, various studies in selected groups have shown incidence of pancytopenia in children from % to 197

3 Sex Male Female Total GENDER Frequency Percent Table 3 Visceral Leishmaniasis Anemia of chronic disorder %.16,17,18 Studies from Europe and Israel have Hemolytic Anemia shown its incidence of 2 new cases per million Myeloid hyperplasia populations.19 These patients usually present with Hypersplenism unexplained pallor, prolonged fever and tendency to Myelodysplastic Syndrome bleed. Its exact etiology is still unknown but autoimmune mechanism has been implicated. World wide studies Congenital Dyserythropoietic have confirmed different pharmaceutical agents as risk factors for development of bone marrow failure.20, 21 Anemia Malaria Infections such as enteric fever, malaria, visceral Hystiocytosis X leishmaniasis and other bacterial infections can result in Gaucher Disease 1.5 pancytopenia in the developing countries.22 Hemophagocytic Syndrome 1.5 Idiopathic thrombocytopenic purpura was the 2nd most common hematological problem encountered in our Bone Marrow secondaries study. It is one of the commonest causes of purpura. Total There may be epistaxis, hematuria and very rarely intracranial bleed which is then fatal.23 Various studies have shown 32% to 48% frequency24, 25 while we found Table 4 hematological disorder present in 11.3% of the cases. it in 15.7% of the cases. This might be due to variable Similar results have been reported in a study from population group and comparatively small sample size. Islamabad 26. Worldwide this is the most common In this study megaloblastic anemia was present in 29 malignancy of childhood 32 accounting for about 41% of (14.6%) of the cases. Similar results have been published all malignancies that occur in children less than 15 years in other national studies.13, 26 The second common of age. In USA the annual incidence of 4.5 cases per deficiency anemia was that of iron deficiency present in children.33 The exact situation in our country is 7.6% of the cases. The same result was present in a study unknown due to lack of large scale studies; however, this from Islamabad.26 This is the most common cause of is the commonest malignant condition in this part of the anemia through out the world.15, 27 Majority of the world as well.26 However the overall incidence in our patients are in the developing countries where it reflects country is lower as compared to the developed countries, the poor socio-economic and nutritional status of the as is the case in India and China.34 The exact etiology of society. People here consume diet grossly deficient in ALL is not known however exposure to herbicides, iron. This has remained a global health problem despite pesticides, chemical solvents and chemical of the efforts to reduce its prevalence.28 Iron deficiency contamination of ground water, viral infection and has an impact on the intellectual development of the radiation are thought to be associated with leukemia. children.29 Therefore growing children should be Recently there has been much insight into the presence of provided with balanced diet. Nutritional megaloblastic chromosomal abnormalities found in most patients with anemia is also one of the leading causes of pancytopenia leukemia. Over the past decade also there has been in younger children.30 substantial improvement in the survival rate of children Megaloblastic anemia usually presents with with leukemia i.e. 80% at five years from diagnosis.35 pancytopenia but rarely may present with Visceral leishmaniasis was reported in 13 (6.6%) of the thrombocytopenia only.25 cases. Majority of these patients were from the hilly areas In our country, green leafy vegetables are abundant of district Dir, Buner, Bajauar and Chitral. The same which are rich sources of folic acid and vitamin B 12. observations have been made in another local study.26 However, other factors like chronic diarrhea, worm's Most of them presented with pallor, prolonged fever and infestations, malabsorption and protein caloric visceromegaly. Interestingly they had a very good malnutrition may be responsible for micronutrient deficiency.31 Leukemia was the most common malignant Disease Aplastic anemia BONE MARROW RESULTS Idiopathic Thrombocytopenic Purpura Megaloblastic Anemia Leukemia Iron Deficiency Anemia Frequency (n=) response to meglumine antimoniate (glocantime). CONCLUSION Bone marrow aplasia/hypoplasia along with Percentage

4 idiopathic thrombocytopenic purpura and Zafar L, Khan DA. Significance of bone deficiency anemia (megaloblastic and iron marrow trephine biopsy in the diagnosis of deficiency) were the commonest non malignant h e m a t o l o g i c a l a n d n o n - h e m a t o l o g i c a l hematological disorders while acute lymphoblastic disorders. Pak J Pathol 2006; 17: leukemia was the most common malignant 13. Rahim F, Ahmed I, Islam S, Hussain M, condition. K h a t t a k TA, B a n o Q. S p e c t r u m o f hematological disorders in children observed REFERENCES i n c o n s e c u t i v e b o n e m a r r o w 1. Miron D, Luder A, Horovitz Y, Izkovitz A, aspirations/biopsies. Pak J Med Sci 2005; 21: Shizgreen I, David EB, et al. Acute human parvovirus B19 infection in hospitalized children: A serologic and molecular survey. 14. Neal S, Young JL, Abkowitz, Luzzatto L. New Pediatr Infect Dis J 2006; 25: Insights into the Pathophysiology of Acquired Cytopenias. Hematology 2000; Lanzkowsky P. Manual of pediatric hematology and oncology 2nd ed. New York: Churchill 15. Issaragrisil S, Leaverton PE, Chansung K, Livingstone, 1995: p Thamprasit T, Porapakham Y, Young SS. The Aplastic Anemia Study Group: The incidence 3. Listernick R. A 14-year-old girl with of aplastic anemia in Thailand. Am J Hematol pancytopenia. Pediar Ann 2006; 35: ; 61: Jadhav MV, Landge MP, Surana S, Sawaimoon 16. Manan M, Kaliq MA, Ahmed S, Qayum I, SK. Gaucher's diseases: Report of 4 cases. Idrees M. Diagnostic significance of Bone Idian J Pathol Microbiol 2007; 50: Marrow examination: A nine years experience. 5. Agarwal S, Narayan S, Sharma S, Kahkashan JAMA 2000; 12: D, Patwari AK. Hemophagocytic syndrome 17. Memon S, Shaikh S, Akbar M, Nizamani A. associated with visceral leishmaniasis. Indian J Etiological spectrum of pancytopenia based on Pediatr 2006; 73: Bone Marrow examination in children. J Coll 6. Ozyurek E, Ozcay F, Yilmaz B, Ozbek N. Physicians Surg Pak 2007; 16: H e m o p h a g o c y t i c l y m p h o h i s t i o c y t o s i s 18. Niazi M, Fazl-i-Raziq. The incidence of associated with visceral leishmaniasis: A case underlying pathology in pancytopenia-an report. Pediatr Hematol Oncol 2005; 22: 409- experience of 89 cases. J Postgrad Med Inst ; 18: Karakukcu M, Patiroglu T, Ozdemir MA, Gunes 19. Young NS. Hematopoietic cell destruction by T, Gumus H, Karakukcu C. Pancytopenia, a immune mechanisms in acquired aplastic rare hematologic manifestation of Brucellosis anemia. Semin Hematol 2000; 37: in children. J Pediatr Hematol Oncol 2004; 26: Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis and 8. Yaldirmak Y, Palnduz A, Telhan L, Arapoglu aplastic anemia. New York: Oxford University M, Kayaalp N. Bone marrow hypoplasia Press; 1991: during Brucella infection. J Pediatr Hematol Oncol 2003; 25: Acharya S, Bussel JB. Hematologic toxicity of sodium valproate. J Pediatr Hematol Oncol 9. Wen JQ, Feng HL, Wang XW, Pang JP. 2000; 22: Hemogram and bone marrow morphology in children with chronic aplastic anemia and 22. Bhatnagar SK, Chandra J, Narayan S, Sharma myelodysplastic syndrome. World J Pediatr S, Singh V, Dutta AR. Pancytopenia in 2008; 4: children: Etiological profile. J Trop Pediatr 2005; 51: Riley RS, Hogan TF, Pavot DR, Forysthe R, Massey D, Smith E, et al. A pathologist's 23. de Alarcon PA. Immune or Idiopathic perspective on bone marrow aspiration and thrombocytopenic purpura in childhood: what biopsy. Performing bone marrow examination. are the risk and who should be treated? J J Clin Lab Anal 2004; 18: Pediatr 2003; 143: Mohanty SK, Dash S. Bone marrow metastasis 24. Ng SC, Kuperan P, Chan KS, Bosco J, Chan in solid tumors. Indian J Pathol Microbiol GL. Megaloblastic Anemia- a review from 2003; 46: University Hospital, Kuala Lumpur. Ann Acad Med Sing 8; 17: Afzal S, Ahmed M, Mubarik A, Khan SA, 199

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